effect of pre-treatment with cromolyn or albuterol on response to pul-042 inhalation solution (pul-042)

Conditions: Healthy

Summary: this study evaluates the effect of pre-treatment with either cromolyn sodium or albuterol sulfate on the safety and tolerability or pul-042 inhalation solution in healthy subjects.

healthy subjects (8 per cohort) will be randomized to either pre-treatment or no pre-treatment (4 per group). the initial cohort will receive pre-treatment with cromolyn sodium. subjects will be followed for 2 weeks for safety and tolerability, undergo a 2 week washout period and then be assigned to the alternative treatment (i.e., subjects who received cromolyn sodium prior to pul-042 inhalation solution will not receive pretreatment) and then followed for an additional 2 weeks. subsequent cohort will receive pre-treatment with albuterol sulfate in a like manner.

Eligibility criteria:
inclusion criteria: * males or females of non-childbearing potential (defined as surgically sterilized \[tubal ligation/hysterectomy/bilateral salpingo oophorectomy or post- menopausal for \> 2 years) with a negative urine human chorionic gonadotropin (hcg) pregnancy test at the screening visit * body mass index (bmi) between 18 and 30 kg/m2 * ability to perform spirometry according to american thoracic society standards * normal spirometry (forced expiratory volume in 1 second \[fev1\] and forced vital capacity \[fvc\] ≥ 80% and ≤ 120% based on predicted values) at the screening visit and at visit 2. * pulse oximetry ≥95% on room air * ability to understand and give informed consent * males willing to practice contraception (condom + spermicide) during the study and for 30 days after completion of the exclusion criteria: * febrile (temperature ≥ 99.5°fahrenheit) * a history of use of any tobacco products during the year prior to the screening visit and a total exposure of \> 5 pack years or a positive urine cotinine level at the screening visit * clinically significant laboratory finding as determined by the principal investigator or designee at the screening visit or at visit 2 * positive test for drugs of abuse (alcohol, cannabinoids, opiates, cocaine, amphetamine, barbiturates, benzodiazepine, phencyclidine) * any active medical problems requiring treatment * subjects who exhibit symptoms of respiratory infection or have experienced respiratory symptoms of an upper respiratory infection within 30 days prior to the screening visit. * history of chronic pulmonary disease (eg, asthma \[including atopic asthma, exercise induced asthma, or asthma triggered by respiratory infection\], pulmonary fibrosis), pulmonary hypertension, or heart failure * any out of range qtc fridericia (qtcf) or other clinically significant ecg findings as determined by the principal investigator or designee at visit 2 or visit 12. * history of atopic reactions * administration of any anti-inflammatory therapy (eg, no steroidal anti-inflammatory drugs or corticosteroids) within 4 weeks prior to randomization or expected to be ongoing during the study * an anticipated need for use of any inhaled medication during the study * intake of coffee, tea, cola drinks, chocolate on days of study visits 1-21 * intake of alcohol, caffeine or strenuous exercise within 72 hours prior to study drug administration or intake of grapefruit within 7 days prior to the administration of study drug * intake of alcohol within 4 hours of spirometry; smoking within 1 hour of spirometry; performing vigorous exercise within 30 minutes of spirometry; wearing clothing that substantially restricts full chest and abdominal expansion; or eating a large meal within 2 hours of spirometry * administration of any over the counter (otc)/prescription medication, supplements, herbals or vitamins within 14 days prior to study drug administration. administration of tylenol within 72 hours of study drug administration (doses up to 2g/day will be allowed prior to 72 hours before study drug administration) * exposure to any investigational agent within 30 days prior to the screening visit * receipt of a flu vaccine in the last 3 months * prior exposure to pul-042 * known positive for human immunodeficiency virus, or on active anti-retroviral therapy and known hepatitis b surface antigen positive or hepatitis c positive

Keywords: safety tolerability